That unilateral spermatic cord torsion has an adverse effect on fertility potential of the male has been widely demonstrated. Clinically, the current treatment is to surgically untwist the affected organ with the hope that any damaged tissues will regenerate and contribute to fertility or at least maintain normal androgen production. However, in recent years our laboratory along with others have shown that unilateral testicular damage adversely affects the contralateral organ. Indeed, we have demonstrated that the presence of a testis damaged by torsion significantly reduced the fertility of male rats when compared to animals that had the damaged organ removed. Recently, evidence has been presented indicating that this effect is mediated by an immune response to the damaged testis, which in turn causes subsequent degeneration of the contralateral testis. We therefore propose to systematically evaluate the efficacy of cyclosporine alone or in combination with prednisone to prevent the subsequent infertility in the male rat following unilateral spermatic cord torsion. We will also assess the effectiveness of these drugs in combination with removal of the damaged organ. During these studies we will determine the serum testosterone concentrations of each male rat and perform detailed histological examination of both the damaged testes and the contralateral testes. These studies will utilize the spermatic cord torsion model with which our laboratory has extensive experience. This model has been chosen for its relative ease and reproducibility. In addition, the assessment of male rat fertility to be used in these studies is a technique developed in our laboratory and permits accurate assessment of both fertility and fecundity as a function of the male. Since our preliminary findings with cyclosporine are significant, it is expected that the present studies will rapidly yield significant information concerning the mechanism of bilateral testicular degeneration in the presence of unilateral damage. We will note the efficacy of cyclosporine and prednisone to prevent contralateral testicular degeneration and the corresponding reduction in male fertility. These studies are considered by us to be the first important step toward eliminating human male infertility subsequent to spermatic cord torsion using temporary immune suppression.